rs10844318

Variant names:

• chr12-32722472-A-G
• rs10844318
• NM_001278464.2:c.957A>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012062.5(DNM1L):​c.918A>G​(p.Thr306Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,612,406 control chromosomes in the GnomAD database, including 15,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1555 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13584 hom.)
• Consequence: DNM1L NM_012062.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.749

Genes affected

DNM1L (HGNC:2973): (dynamin 1 like) This gene encodes a member of the dynamin superfamily of GTPases. The encoded protein mediates mitochondrial and peroxisomal division, and is involved in developmentally regulated apoptosis and programmed necrosis. Dysfunction of this gene is implicated in several neurological disorders, including Alzheimer's disease. Mutations in this gene are associated with the autosomal dominant disorder, encephalopathy, lethal, due to defective mitochondrial and peroxisomal fission (EMPF). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 12-32722472-A-G is Benign according to our data. Variant chr12-32722472-A-G is described in ClinVar as [Benign]. Clinvar id is 260168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.749 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM1L	NM_001278464.2	c.957A>G	p.Thr319Thr	synonymous_variant	Exon 10 of 21	ENST00000553257.6	NP_001265393.1
DNM1L	NM_012062.5	c.918A>G	p.Thr306Thr	synonymous_variant	Exon 9 of 20	ENST00000549701.6	NP_036192.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM1L	ENST00000553257.6	c.957A>G	p.Thr319Thr	synonymous_variant	Exon 10 of 21	2	NM_001278464.2	ENSP00000449089.1
DNM1L	ENST00000549701.6	c.918A>G	p.Thr306Thr	synonymous_variant	Exon 9 of 20	1	NM_012062.5	ENSP00000450399.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21495 AN: 152092 Hom.: 1551 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0735

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0892

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.152

GnomAD3 exomes AF: 0.123 AC: 30841 AN: 250954 Hom.: 2021 AF XY: 0.125 AC XY: 16993 AN XY: 135656

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.0779

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.0769

Gnomad SAS exome AF: 0.111

Gnomad FIN exome AF: 0.0970

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.135

GnomAD4 exome AF: 0.134 AC: 195843 AN: 1460196 Hom.: 13584 Cov.: 32 AF XY: 0.134 AC XY: 97565 AN XY: 726412

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.0838

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.0708

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.141 AC: 21500 AN: 152210 Hom.: 1555 Cov.: 32 AF XY: 0.139 AC XY: 10335 AN XY: 74438

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0737

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0892

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.150

Alfa AF: 0.138 Hom.: 1072

Bravo AF: 0.146

Asia WGS AF: 0.105 AC: 366 AN: 3476

EpiCase AF: 0.149

EpiControl AF: 0.154

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Feb 22, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Optic atrophy 5 Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.6
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10844318; hg19: chr12-32875406; COSMIC: COSV56772893; COSMIC: COSV56772893;